"introduction To Metabolism"

Front 1

What is the "fed" state?

Back 1

--During and immediately after a meal
--Use nutrients to provide energy
--Store the extra energy as fuel stores.

Front 2

When you eat something, what happens to the different components?

Back 2

--Dietary Carbs-->monosaccharides-->GLUCOSE
--Dietary Protein-->AMINO ACIDS
--Dietary Lipid (Fat)-->CHYLOMICRONS

Front 3

What happens in liver during fed state?

Back 3

FED STATE-->Liver DIGESTS glucose.

FATES OF GLUCOSE
--either OXIDIZE glucose or convert it to GLYCOGEN and TRIACYLGLYCEROLS

OXIDIZE GLUCOSE
--Glycolysis
GLUCOSE-->pyruvate-->acetyl Coa-->TCA-->ETC-->ATP!

CONVERT GLUCOSE
--Glycogen synthesis
GLUCOSE-->glycogen

GLUCOSE-->pyruvate-->FA + glycerol (lipogenesis)-->TRIACYLGLYCEROLS-->leave liver as VLDL's

FATES OF AMINO ACIDS
A.ACIDS-->proteins (translation)
A.ACIDS-->urea

Front 4

What happens in brain during fed state?

Back 4

OXIDIZE GLUCOSE
--Glycolysis
GLUCOSE-->pyruvate-->acetyl Coa-->TCA-->ETC-->ATP

-->glucose is only fuel that crosses blood/brain barrier!

Front 5

What happens in RBC during fed state?

Back 5

OXIDIZE GLUCOSE
--Glycolysis
GLUCOSE-->pyruvate-->lactate

-Have ABSOLUTE dependence on glucose, because they LACK mitochondria (can't do pyruvate oxidation, TCA, oxidative phosphorylation)--only energy from glucose)

Front 6

What is CORI cycle?

Back 6

Lactate generated from anaerobic glycolysis in RBC is carried back to liver-->converted into pyruvate

--pyruvate can either: enter TCA cycle (if liver needs energy) or be stored as glycogen (if liver doesn't need energy)

Front 7

What happens in muscle during fed state?

Back 7

OXIDIZE GLUCOSE
--Glycolysis
GLUCOSE-->pyruvate-->LACTATE or ATP
(both oxidative and anaerobic processes)

STORE GLUCOSE
--Glycogen synthesis
Extra GLUCOSE-->glycogen

Front 8

What happens to fats in liver during the fed state?

Back 8

EXCESS GLUCOSE
--De novo lipogenesis
GLUCOSE-->converted to FA's + Glycerol-->Triacylglycerol (TAG)-->VLDL's-->released into blood-->stored in adipose cells OR broken down by muscle for energy

Front 9

What happens to fats in muscle and adipose cells during fed state?

Back 9

TAGs are in Chylomicrons (comes from dietary fat) AND VLDL's (made from lipogenesis in liver)

--Chylomicrons travel to tissue-->TAG's are broken down into glycerol and FFA
--VLDL's are transported to muscle or adipose tissue and serve similar purpose as chylomicron TAGs.

Adipose
--FFA are collected-->TAGs reformed.
--ALSO adipose tissue can convert glucose-->TAGS by de novo lipogenesis.

Muscle
--FFA-->Acetyl Coa (Beta oxidation)-->TCA-->oxidative phosphorylation.

Front 10

BIG picture--what are the major metabolic events in fed state?

Back 10

1) LIVER uses GLUCOSE and AMINO ACIDS for energy needs and conversion into glycogen, fat, protein (glycolysis, glycogen synthesis, de novo lipogenesis, translation)

2) BRAIN oxidizes GLUCOSE to make energy (glycolysis)

3) RBC's convert GLUCOSE-->LACTATE (anaerobic glycolysis-->CORI cycle)

4) MUSCLE converts GLUCOSE to LACTATE (anaerobic glycolysis) or CO2 (glycolysis). Converts FFA into CO2 (B-oxidation). Extra glucose-->glycogen (glycogenolysis)

5) ADIPOSE stores TAG.

Front 11

What is the "fasted" state?

Back 11

--Few hours after a meal.
--Have used up all the dietary nutrients for energy OR stored them.
--Now, you need to use STORES to meet ENERGY NEEDS.
--Most importantly--need to provide GLUCOSE to the BRAIN and RBC, because it's all they have.

Front 12

What hormones initiate "fasting" state?

Back 12

--Decreased insulin secretion, increased glucagon secretion!

Front 13

What happens in liver during fasting state?

Back 13

FASTING STATE-->Liver PRODUCES glucose for the rest of the body

Glycogenolysis
--Glycogen stores-->GLUCOSE-->RELEASED to BRAIN and RBC's

Gluconeogenesis
--CORI cycle returns LACTATE to liver from RBC-->converted to GLUCOSE-->RELEASED to BRAIN, RBC's.

Beta Oxidation
FFA-->Acetyl Coa-->TCA-->oxidative phosphorylation (ETC)-->ATP!
(Eventually, KETOGENESIS occurs. Acetyl Coa-->KB's)

Front 14

What happens in muscle during fasting state?

Back 14

Proteolysis/gluconeogenesis
--Muscle protein broken down (proteolysis)-->releases alanine-->goes to liver (alanine cycle)-->converted to GLUCOSE (gluconeogenesis)

--Proteolysis also releases glutamine-->supports nucleotide synthesis in dividing tissues-->creates alanine-->goes to liver-->converted to GLUCOSE (gluconeogenesis)

Beta oxidation
FFA-->Acetyl Coa-->TCA-->oxidative phosphorylation (ETC)-->ATP!

Front 15

What happens in adipose tissue during fasting state?

Back 15

Lipolysis
--TAGS-->GLYCEROL+FFA

FFA-->used in beta oxidation

GLYCEROL-->used in liver for gluconeogenesis.

Front 16

What is ketogenesis?

Back 16

--During long fast, too much acetyl Coa is made by beta-oxidation-->can no longer enter TCA cycle.
--excess acetyl Coa-->ketone bodies!
-->can generate energy in brain and muscle-->spares glucose for RBC, which NEEDS it.

Front 17

How are delta-G and delta-G* computed?

How do they affect whether biochemical reactions occur?

Back 17

delta G=delta-G*+RTln[products]/[reactants]

delta-G*=-RTlnKeq
--delta-G* is a CONSTANT-->measure of INHERENT ability of reactants to make products. (Keq is measured in test tube w/fixed amount of products, reactants-->rxn allowed to go to completion, then determine rxn specifics
-->if Keq>1, delta-G* is negative-->makes delta-G negative-->exergonic!
-->if Keq=<1, delta-G* is positive-->makes delta-G positive-->endergonic!

Front 18

If a reaction is energetically unfavorable, how can you get it to occur?

Back 18

--Need your delta-G to be negative
--Overall, reactions are additive-->so..can couple reactions w/ATP hydrolysis to make an OVERALL negative delta-G*-->makes a negative delta-G-->spontaneous rxn
-->can also use substrate level phosphorylation to make ATP. High energy phosphate bond on another molecule is cleaved, releasing energy, which drives endergonic formation of ATP.

Front 19

What are roles of NAD, NADP, FAD, and CoA in metabolism?

Back 19

-->electrons/protons are removed and transferred to NAD+, NADP+, FAD+-->forms NADH, NADPH, FADH-

NADH/FADH--> dump their electrons/protons into ETC-->make ATP!

NADPH-->gives up electrons/protons to produce reducing equivalents to make macromolecules and neutralize oxygen species.

CoA-->another important carrier in metabolism.
-->Acetic and fatty acids not v. reactive-->bound to CoA->forms acetyl CoA and acyl CoA-->SUPER reactive!

Front 20

What are ways that metabolic pathways are regulated?

Back 20

1) reversible phosphorylatio-->add (kinase) or remove (phosphatase) to/from serine, threonine, or tyrosine-->can ACTIVATE or INACTIVATE enzyme.

2) allosteric regulation-->small molecules bind to enzyme-->alter activity
3) change enzyme level-->signals will increase synthesis of enzymes when they need them in pathways (induction) or turn off production if they're not needed (repression)
4) compartmentalization-->pathways can use COMMON intermediates-->keep these substrates separate (different compartments) to decrease competition for intermediates.

Front 21

What is glycolysis?

Back 21

glucose-->pyruvate (aerobic)
glucose-->lactate (anaerobic)

fates:
pyruvate-->fat (lipogenesis)
pyruvate-->acetyl Coa-->TCA-->oxidative phosphorylation (oxidation)

Front 22

What is lipolysis?

Back 22

hydrolysis of stored TAGs-->FFA+glycerol-->transported to tissues for energy generation

Front 23

What is glycogenolysis?

Back 23

glycogen-->glucose

Front 24

What is beta-oxidation?

Back 24

oxidation of FFA-->produces acetyl CoA in the mitochondria

Front 25

What is proteolysis?

Back 25

Breakdown of proteins into a.acids-->used in gluconeogenesis

Front 26

What is ketogenesis?

Back 26

Acetyl Coa-->ketone bodies